Economic impact model of delayed inhibitor development in patients with hemophilia a receiving emicizumab for the prevention of bleeding events

Abstract

Aims: Cumulative exogenous factor VIII (FVIII) exposure is an important predictor of developing neutralizing antibodies (inhibitors) to FVIII in patients with persons with hemophilia A (PwHA). The aim of this study was to model the costs of emicizumab versus FVIII prophylaxis and total treatment costs for patients with severe HA.Materials and Methods: An Excel-based decision model was developed to calculate cumulative costs in PwHA over a 20-year time horizon from the US payer perspective. The model considered persons with severe HA beginning at age 12 months with no prior FVIII exposure and initiating prophylaxis with emicizumab or FVIII. PwHA could develop inhibitors on accumulation of 20 FVIII exposure days. PwHA with inhibitors replaced FVIII with bypassing agents until inhibitors resolved spontaneously, following immune tolerance induction (ITI), or at the end of the time horizon. The primary model outcome was the difference in emicizumab versus FVIII treatment costs in 2019 USD. Sensitivity analyses were performed to test the robustness of results.Results: Total incremental cost over 20 years was -$1,945,480 (emicizumab arm, $4,919,058; FVIII arm, $6,864,538). Prophylaxis costs (emicizumab arm, $4,096,105; FVIII arm, $6,290,919) comprised the majority of costs in both groups, followed by breakthrough bleed treatment for the FVIII arm ($342,652) and ITI costs for the emicizumab arm ($733,671). Higher costs in the FVIII group reflected earlier inhibitor development (FVIII, 4 months; emicizumab, 162 months) and switch to bypassing agents.Limitations: The model design reflects a simplified treatment pathway for patients with severe HA who initiate FVIII or emicizumab prophylaxis. In the absence of clinical data, a key conservative assumption of the model is that patients receiving emicizumab and FVIII prophylaxis have the same risk of developing inhibitors.Conclusions: This study suggests that prophylaxis with emicizumab results in cost savings compared to FVIII prophylaxis in HA.

Keywords: C51; Factor VIII; Hemophilia A; I10; emicizumab; health economics; inhibitors.